Sarcoma,Soft TissuePhase 1SeliSarcNCT04595994
Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma
A Phase 1 study testing Selinexor in people with Sarcoma,Soft Tissue, run by Grupo Espanol de Investigacion en Sarcomas at 6 sites in Spain.
Trial summary
Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sarcoma,Soft Tissue
- What is being tested?
- Selinexor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 6 sitesSpain
- Study dates
- 2 Sep 2020to 31 May 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must provide written informed consent prior to performance of any study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. imaging tests), obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
- Age: 18-80 years
- Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft part sarcoma) or osteosarcoma confirmed by central pathology review prior to enrolment with an archive tumor sample. A fresh paraffin embedded tumor tissue block must be provided for all subjects for biomarker analysis before and (when feasible) after treatment with investigational products.
- Metastatic/advanced disease in progression in the last 6 months.
- Patients have previously received at least one previous line of systemic therapy
- Measurable disease according to RECIST 1.1 criteria.
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- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Adequate hepatic, renal, cardiac, and hematologic function.
- Laboratory tests as follows:
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine ≤ 1.5 mg/dL
- Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.
- Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment and agree to use birth control measures during study treatment and for 3 months after its completion. Patients must not be pregnant or nursing at study entry. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
Who cannot join
- Three or more previous lines of chemotherapy
- Prior selinexor or another XPO1 inhibitor treatment.
- Administration of a previous gemcitabine-containing treatment.
- Any concurrent medical condition or disease (e.g. uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
- Pregnant or breastfeeding females.
Show all 13Show fewer
- Body surface area (BSA) <1.4 m2 at baseline, calculated by the Du Bois(31) or osteller(32) method.
- Life expectancy of less than 3 months.
- Major surgery within 4 weeks prior to C1D1.
- Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.
- Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the NCCN CPGO for antiemesis and anorexia/cachexia (palliative care).
- Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
- Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible).
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites, 5 recruiting
- Active, not recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
- Recruiting
HU Vall d'Hebron
Barcelona, 08035
Claudia Valverde, MD, cmvalver@vhebron.net
- Recruiting
H. Fundación Jiménez Díaz
Madrid, 28040
Javier Martín Broto, MD, jmartin@atbsarc.org
Javier Martín Broto, MD
- Recruiting
Hospital Clínico San Carlos
Madrid, 28040
Antonio Casado, MD, antoniocasado6@gmail.com
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
Andrés Redondo, MD, aredondo12@gmail.com
- Recruiting
Hospital Universitario Miguel Servet
Zaragoza, 50009
Javier Martínez Trufero, MD
jmtrufero@seom.org
About this study
Official title: Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma
Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.
Read the detailed description
Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.
In the Phase I part safety and toxicity of the combination will be assessed using a 3+3 design. The recommended dose for the Phase II will be determined.
In the Phase II part there will be 4 different cohorts:
Cohort 1: Undifferentiated pleomorphic sarcoma (UPS) Cohort 2: Leiomyosarcoma (LMS) Cohort 3: Alveolar soft-part sarcoma (ASPS) Cohort 4: Osteosarcoma Patients will be randomized for phase II part only (except in cohort 3) in an open-label way to receive selinexor in combination with gemcitabine versus gemcitabine alone
- Conditions
- Sarcoma,Soft Tissue
- Being tested
- Selinexor
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called Gemcitabine
For both interventional ( Selinexor and Gencitabine) Dose-limiting toxicity (DLT) will be applied only to either of the following toxicities occurring during the first treatment cycle (days 1-21).
| Study group | Role | What they receive |
|---|---|---|
| Selinexor + Gemcitabine | Experimental | Dose escalation levels (Phase I):
All included patients will take both drugs:
Selinexor weekly (given on days 1,8 and 15 of each cycle) will be dispensed at different dose levels: dose level 1:60 mg, dose level 2: 60 mg, dose level 3: 60 mg, and dose level 4: 80 mg).
Gemcitabine weekly (given on days 1, 8 of each cycle) will be administered at different dose levels: (dose level 1:1000 mg/m2 (30 min), dose level 2:1000 mg/m2 (10 mg/m2/min), dose level 3:1200 mg/m2 (10 mg/m2/min) and dose level 4: 1200 mg/m2 (10 mg/m2/min)).
Selinexor: tablet (20 mg tablets) Oral use.
Gemcitabine: Concentrate for solution for infusion. Intravenous use. Receives: Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
To determine the maximum tolerated dose (MTD) or the recommended dose for phase II of Selinexor plus gemcitabine.
Measured: 6 months
Secondary outcomes (5)
Safety profile according to CTCAE 5.0.
Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests.
Measured: 6 months
Objective response rate (ORR).
Objective Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 criteria).
Measured: 6 months
Evaluate efficacy according to Choi response
Efficacy measured through tumor response according to Choi criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression.
Measured: 6 months
Patients's quality of life (QoL)
Quality of life will be measured with European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire 30
Measured: 6 months
Pharmacokinetic values in blood analysis
Impact of pharmacokinetics. interactions between selinexor in gemcitabine
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start2 Sep 2020
- Primary completion30 Nov 2025 (estimated)
- Study completion31 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sarcoma,Soft TissueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- unique arms for each possible dose
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Investigacion en Sarcomas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Javier Martín Broto, MD, Study director, Hospital Fundación Jiménez Díaz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04595994
- Sponsor's protocol ID
- GEIS-67
- Other IDs
- 2019-000652-33, 2019
- Acronym
- SeliSarc
- Status last verified
- Jan 2024
- First submitted
- 8 Oct 2020
- Last updated
- 23 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kashyap T, Argueta C, Unger T, Klebanov B, Debler S, Senapedis W, Crochiere ML, Lee MS, Kauffman M, Shacham S, Landesman Y. Selinexor reduces the expression of DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents. Oncotarget. 2018 Jul 20;9(56):30773-30786. doi: 10.18632/oncotarget.25637. eCollection 2018 Jul 20.
PubMed 30112106Park KS, Han BG, Lee KH, Kim DS, Kim JM, Jeon H, Kim HS, Suh SW, Lee EH, Kim SY, Lee BI. Depletion of nucleophosmin via transglutaminase 2 cross-linking increases drug resistance in cancer cells. Cancer Lett. 2009 Feb 18;274(2):201-7. doi: 10.1016/j.canlet.2008.09.007. Epub 2008 Oct 11.
PubMed 18851895Hill R, Rabb M, Madureira PA, Clements D, Gujar SA, Waisman DM, Giacomantonio CA, Lee PW. Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy. Cell Death Dis. 2013 Sep 5;4(9):e791. doi: 10.1038/cddis.2013.307.
PubMed 24008735Martin-Broto J, Casado A, Marquina G, Redondo A, Martinez-Trufero J, Valverde C, Gutierrez A, Bernabeu D, Ortega L, Merino J, Ramos R, Ledesma P, Mondaza-Hernandez JL, Moura DS, Hindi N. Gemcitabine plus selinexor in selective advanced sarcomas: a phase I of the Spanish group for research on sarcoma study. Nat Commun. 2026 Jan 20;17(1):1873. doi: 10.1038/s41467-026-68729-1.
PubMed 41559089
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma
- ClinicalTrials.gov ID
- NCT04595994
- Acronym / sponsor ID
- SeliSarc / GEIS-67
- Conditions
- Sarcoma,Soft Tissue
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Grupo Espanol de Investigacion en SarcomasUniversity, hospital or other
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- 30 Nov 2025 (estimated)
- Study completion
- 31 May 2026 (estimated)
- First posted
- 22 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.
Detailed description
Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.
In the Phase I part safety and toxicity of the combination will be assessed using a 3+3 design. The recommended dose for the Phase II will be determined.
In the Phase II part there will be 4 different cohorts:
Cohort 1: Undifferentiated pleomorphic sarcoma (UPS) Cohort 2: Leiomyosarcoma (LMS) Cohort 3: Alveolar soft-part sarcoma (ASPS) Cohort 4: Osteosarcoma Patients will be randomized for phase II part only (except in cohort 3) in an open-label way to receive selinexor in combination with gemcitabine versus gemcitabine alone
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- unique arms for each possible dose
| Arm | Type | Receives |
|---|---|---|
| Selinexor + Gemcitabine | Experimental | Drug: SelinexorDose escalation levels (Phase I): All included patients will take both drugs: Selinexor weekly (given on days 1,8 and 15 of each cycle) will be dispensed at different dose levels: dose level 1:60 mg, dose level 2: 60 mg, dose level 3: 60 mg, and dose level 4: 80 mg). Gemcitabine weekly (given on days 1, 8 of each cycle) will be administered at different dose levels: (dose level 1:1000 mg/m2 (30 min), dose level 2:1000 mg/m2 (10 mg/m2/min), dose level 3:1200 mg/m2 (10 mg/m2/min) and dose level 4: 1200 mg/m2 (10 mg/m2/min)). Selinexor: tablet (20 mg tablets) Oral use. Gemcitabine: Concentrate for solution for infusion. Intravenous use. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must provide written informed consent prior to performance of any study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. imaging tests), obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
- Age: 18-80 years
- Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft part sarcoma) or osteosarcoma confirmed by central pathology review prior to enrolment with an archive tumor sample. A fresh paraffin embedded tumor tissue block must be provided for all subjects for biomarker analysis before and (when feasible) after treatment with investigational products.
- Metastatic/advanced disease in progression in the last 6 months.
- Patients have previously received at least one previous line of systemic therapy
Key exclusion criteria (13 listed)
- Three or more previous lines of chemotherapy
- Prior selinexor or another XPO1 inhibitor treatment.
- Administration of a previous gemcitabine-containing treatment.
- Any concurrent medical condition or disease (e.g. uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelinexorAlso: GemcitabineFor both interventional ( Selinexor and Gencitabine) Dose-limiting toxicity (DLT) will be applied only to either of the following toxicities occurring during the first treatment cycle (days 1-21). | Drug | Selinexor + Gemcitabine |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: 6 months
To determine the maximum tolerated dose (MTD) or the recommended dose for phase II of Selinexor plus gemcitabine.
5 secondary outcomes
Safety profile according to CTCAE 5.0.
Time frame: 6 months
Objective response rate (ORR).
Time frame: 6 months
Evaluate efficacy according to Choi response
Time frame: 6 months
Patients's quality of life (QoL)
Time frame: 6 months
Pharmacokinetic values in blood analysis
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Background: PubMed 30112106Kashyap T, Argueta C, Unger T, Klebanov B, Debler S, Senapedis W, Crochiere ML, Lee MS, Kauffman M, Shacham S, Landesman Y. Selinexor reduces the expression of DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents. Oncotarget. 2018 Jul 20;9(56):30773-30786. doi: 10.18632/oncotarget.25637. eCollection 2018 Jul 20.
- Background: PubMed 18851895Park KS, Han BG, Lee KH, Kim DS, Kim JM, Jeon H, Kim HS, Suh SW, Lee EH, Kim SY, Lee BI. Depletion of nucleophosmin via transglutaminase 2 cross-linking increases drug resistance in cancer cells. Cancer Lett. 2009 Feb 18;274(2):201-7. doi: 10.1016/j.canlet.2008.09.007. Epub 2008 Oct 11.
- Background: PubMed 24008735Hill R, Rabb M, Madureira PA, Clements D, Gujar SA, Waisman DM, Giacomantonio CA, Lee PW. Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy. Cell Death Dis. 2013 Sep 5;4(9):e791. doi: 10.1038/cddis.2013.307.
- Derived from this study: PubMed 41559089Martin-Broto J, Casado A, Marquina G, Redondo A, Martinez-Trufero J, Valverde C, Gutierrez A, Bernabeu D, Ortega L, Merino J, Ramos R, Ledesma P, Mondaza-Hernandez JL, Moura DS, Hindi N. Gemcitabine plus selinexor in selective advanced sarcomas: a phase I of the Spanish group for research on sarcoma study. Nat Commun. 2026 Jan 20;17(1):1873. doi: 10.1038/s41467-026-68729-1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Javier Martín Broto, MD study director
Hospital Fundación Jiménez Díaz
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selinexor in people with Sarcoma,Soft Tissue, run by Grupo Espanol de Investigacion en Sarcomas at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Patricio Ledesma (971 439 900 ext. +34, ensayos@sofpromed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04595994, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.